The goal of this research is to define the molecular, cellular, and systems neuroscience that provides the basis for active forgetting. This area of learning and memory research has been overlooked and yet, there is every reason to believe that the processes underlying active forgetting are as complicated and important as learning itself and the stabilization of memories by consolidation. The research project utilizes the model system Drosophila melanogaster because of the ease with which the fly can be conditioned using olfactory cues, the numerous genetic and molecular tools available, and the ability to peer into the brain of living animals and watch the activity of different sets of neurons. The latter approach, functional cellular imaging, employs flies carrying transgenes that express reporters for calcium influx, synaptic transmission, or other neuronal events, to monitor changes in neuronal response properties among the expressing neurons before and after conditioning. Our prior studies using this technique demonstrated that dopamine neurons exhibit ongoing activity after the learning event itself and that this activity likely provides a forgetting signal to the postsynaptic mushroom body neurons. We will extend these studies in several different ways to help understand the mechanistic basis for active forgetting. There is a rich medical importance to this research given the well- documented problems of cognition associated with numerous neuropsychiatric disorders.